Sheik Humarr Khan

Undiagnosed acute viral febrile illnesses, Sierra Leone.

Various arthropod-borne and hemorrhagic fever viruses should be considered when Lassa fever is suspected.

Review of the Literature and Proposed Guidelines for the Use of Oral Ribavirin as Postexposure Prophylaxis for Lassa Fever

Abstract Lassa fever is an acute viral hemorrhagic illness; the virus is endemic in West Africa and also of concern with regard to bioterrorism. Transmission of Lassa virus between humans may occur through direct contact with infected blood or bodily secretions. Oral administration of the antiviral drug ribavirin is often considered for postexposure prophylaxis, but no systematically collected data or uniform guidelines exist for this indication. Furthermore, the relatively low secondary attack rates for Lassa fever, the restriction of the area of endemicity to West Africa, and the infrequency of high-risk exposures make it unlikely that controlled prospective efficacy trials will ever be possible. Recommendations for postexposure use of ribavirin can therefore be made only on the basis of a thorough understanding and logical extrapolation of existing data. Here, we review the pertinent issues and propose guidelines based on extensive review of the literature, as well as our experience in this field. We recommend oral ribavirin postexposure prophylaxis for Lassa fever exclusively for definitive high-risk exposures. These guidelines may also serve for exposure to other hemorrhagic fever viruses susceptible to ribavirin.

Ribavirin for Lassa Fever Postexposure Prophylaxis

To the Editor: Lassa fever is an acute, viral, hemorrhagic illness endemic to West Africa. Intravenous ribavirin drastically reduces deaths from Lassa fever (1). During outbreaks, oral ribavirin is often considered for postexposure prophylaxis (PEP), but no systematically collected data exist for this indication of drug use (1–5). We therefore conducted a retrospective follow-up study to examine adherence and adverse effects associated with oral ribavirin given as PEP during an outbreak of Lassa fever in Sierra Leone in 2004 (6). During this outbreak, family members and some healthcare workers who had direct contact with patients did not use personal protective equipment and were subsequently prescribed oral ribavirin as PEP (200 mg capsules; Schering-Plough Corporation, Kenilworth, NJ, USA). Approximately 3 months after the possible exposures, we surveyed 23 (92%) of 25 persons known to have been prescribed ribavirin PEP. Respondents were asked about demographics, medical history, details of possible exposure to Lassa virus (LASV), dosage and duration of ribavirin prescribed and taken, and use of concomitant medications. When possible, serum was obtained and tested by ELISA for LASV-specific immunoglobulin (Ig) M and IgG (7). The mean age of the 23 respondents was 38 years (range 23–73 years); 14 (61%) were male, 17 (74%) had been exposed at home (during bathing, cleaning, and feeding of family members with Lassa fever), and 6 (26%) had had in-hospital contact with blood and bodily fluids. No needle-stick injuries were reported. All respondents had begun taking oral ribavirin within 2 days after exposure. The drug was prescribed at a mean dose of 800 mg 1×/d (most often as 400 mg 2×/d) for 10 days; however, respondents reported actually taking 400–1,200 mg/d. Only 10 (43%) completed the full 10 days of therapy; mean duration of therapy was 8 days (range 1–14 days). No correlation was found between the prescribed daily dose of ribavirin and the likelihood of completing therapy (p = 0.60). Therapy was completed by 6 (38%) of the 16 (70%) respondents who reported having experienced minor adverse effects and by 4 (57%) of the 7 who reported not having experienced adverse effects (Figure). Many respondents reported having had symptoms even before beginning ribavirin, suggesting at least a partial psychosomatic or other etiology. No correlation was found between likelihood of adverse effects and age (p = 0.18), sex (p = 0.16), or place of exposure (p = 0.63). Six (26%) respondents reported having premorbid health conditions (gastric ulcers, n = 3; gastroesophageal reflux disease, n = 2; hypertension, n = 1), and 15 (65%) took medications in addition to ribavirin during the postexposure period, including paracetamol, folic acid, multivitamins, iron, antacids, antimalarial drugs, antimicrobial drugs, and nonsteroidal anti-inflammatory drugs. Figure Adverse effects reported by 23 persons who took oral ribavirin prophylactically after potential exposure to Lassa virus, Sierra Leone, 2004. Minor adverse effects from oral ribavirin PEP, either biologic or psychosomatic, were frequently noted and decreased adherence. Many of the same adverse effects have been reported (8). Because interviews in our study were conducted months after medication had been taken, recall bias may have occurred. However, 11 (85%) of the 13 repondents who reported not completing therapy could show the interviewer their leftover ribavirin capsules, thus validating their reports. The observational nature of our study prevented us from establishing a causal association between taking ribavirin and the reported adverse effects. Other factors, especially the anxiety often associated with possible LASV exposure, likely contributed to the noted symptoms. Although we cannot exclude the possibility of asymptomatic infection, we found no evidence of secondary transmission of LASV among the respondents. One person reported having fever and malaise after exposure, but test results for LASV were negative. Only 8 (35%) persons consented to follow-up laboratory testing, probably because most did not think it was necessary because of lack of symptoms; all 8 were LASV IgM negative. The duration of IgM after LASV infection has not been well characterized, and antibodies could have cleared in the 3 months between exposure and testing (7). Another possibility is that swift administration of ribavirin blunted the antibody response. Although not studied in humans, total Ig titers in LASV-infected, ribavirin-treated monkeys eventually reached titers similar to those in untreated monkeys (9). Three persons were LASV IgG positive, indicating past exposure. All 3 had other risk factors for infection in addition to their recent exposure, including residence in a Lassa fever– hyperendemic area (all 3) and occupation as healthcare workers (2 of 3). The limitations inherent in our study are its small sample size and retrospective, uncontrolled design. Considering the relatively low secondary attack rate, the restriction of LASV endemicity to remote areas of West Africa, and the infrequency of high-risk exposures, controlled trials for ribavirin PEP in Lassa fever will probably never be possible. Experiences in the field must therefore be used to inform future decisions with regard to use of ribavirin for this indication. Use of oral ribavirin PEP for Lassa fever is likely to be challenging because of poor adherence and adverse effects.

Using modelling to disentangle the relative contributions of zoonotic and anthroponotic transmission: the case of lassa fever.

Background Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. Methodology/Principal Findings Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) , with a maximum value up to . Conclusions/Significance This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.

Multiple Circulating Infections Can Mimic the Early Stages of Viral Hemorrhagic Fevers and Possible Human Exposure to Filoviruses in Sierra Leone Prior to the 2014 Outbreak

Lassa fever (LF) is a severe viral hemorrhagic fever caused by Lassa virus (LASV). The LF program at the Kenema Government Hospital (KGH) in Eastern Sierra Leone currently provides diagnostic services and clinical care for more than 500 suspected LF cases per year. Nearly two-thirds of suspected LF patients presenting to the LF Ward test negative for either LASV antigen or anti-LASV immunoglobulin M (IgM), and therefore are considered to have a non-Lassa febrile illness (NLFI). The NLFI patients in this study were generally severely ill, which accounts for their high case fatality rate of 36%. The current studies were aimed at determining possible causes of severe febrile illnesses in non-LF cases presenting to the KGH, including possible involvement of filoviruses. A seroprevalence survey employing commercial enzyme-linked immunosorbent assay tests revealed significant IgM and IgG reactivity against dengue virus, chikungunya virus, West Nile virus (WNV), Leptospira, and typhus. A polymerase chain reaction-based survey using sera from subjects with acute LF, evidence of prior LASV exposure, or NLFI revealed widespread infection with Plasmodium falciparum malaria in febrile patients. WNV RNA was detected in a subset of patients, and a 419 nt amplicon specific to filoviral L segment RNA was detected at low levels in a single patient. However, 22% of the patients presenting at the KGH between 2011 and 2014 who were included in this survey registered anti-Ebola virus (EBOV) IgG or IgM, suggesting prior exposure to this agent. The 2014 Ebola virus disease (EVD) outbreak is already the deadliest and most widely dispersed outbreak of its kind on record. Serological evidence reported here for possible human exposure to filoviruses in Sierra Leone prior to the current EVD outbreak supports genetic analysis that EBOV may have been present in West Africa for some time prior to the 2014 outbreak.

Understanding the Emergence of Ebola Virus Disease in Sierra Leone: Stalking the Virus in the Threatening Wake of Emergence

Since Ebola Virus Disease (EVD) was first identified in 1976 in what is now the Democratic Republic of Congo, and despite the numerous outbreaks recorded to date, rarely has an epidemic origin been identified. Indeed, among the twenty-one most documented EVD outbreaks in Africa, an index case has been identified four times, and hypothesized in only two other instances. The initial steps of emergence and spread of a virus are critical in the development of a potential outbreak and need to be thoroughly dissected and understood in order to improve on preventative strategies. In the current West African outbreak of EVD, a unique index case has been identified, pinpointing the geographical origin of the epidemic in Guinea. Herein, we provide an accounting of events that serve as the footprint of EVD emergence in Sierra Leone and a road map for risk mitigation fueled by lessons learned.

Human-monoclonal-antibody therapy protects nonhuman primates against advanced Lassa fever

There are no approved treatments for Lassa fever, which is endemic to the same regions of West Africa that were recently devastated by Ebola. Here we show that a combination of human monoclonal antibodies that cross-react with the glycoproteins of all four clades of Lassa virus is able to rescue 100% of cynomolgus macaques when treatment is initiated at advanced stages of disease, including up to 8 d after challenge.

The voluntary HIV counselling and testing service in Kenema District, Sierra Leone, 2004-2006: a descriptive study.

BackgroundVoluntary counselling and testing (VCT) is an important component of national HIV programs, which are necessary to realize the right to health. VCT data also provide valuable information on regional HIV epidemiology.MethodsThe study examines data on the population that obtained HIV VCT in Kenema District, Sierra Leone, from 2004 to 2006, using descriptive statistics and exploring potential HIV risk factors using bivariate and multivariable logistic regression. Analysis was performed separately for two subpopulations: those accessing VCT routinely as part of antenatal care and those specifically seeking VCT.ResultsDuring this period, 2230 people accessed VCT: 1213 through antenatal testing and 1017 specifically seeking VCT. The HIV prevalence was 0.6% in women presenting for antenatal care, 12.6% in women specifically accessing VCT, and 6.7% in men specifically accessing VCT. In both bivariate and multivariable analyses, being female was statistically significantly associated with testing positive in people specifically seeking VCT.ConclusionsThese data from the VCT service in Kenema will be used to improve the accessibility of HIV testing. Questions raised by the analysis will be used to enhance data collection and to inform further research on risk factors.

Prevalence of HIV-2 and ART treatment coverage in Northern Sierra Leone

Acquired immunodeficiency syndrome caused by HIV-1 or HIV-2, affects 35.3 million people worldwide. Nine HIV-2 subtypes originating from sooty mangabeys in West Africa have been described. Subtypes A and B are epidemic while C to I are crossovers that are known in single persons. HIV-2F is an exception among non-epidemic subtypes, being pathogenic and found in two persons, both from Northern Sierra Leone, suggesting transmissibility. Very little data are published concerning the distribution and prevalence of HIV2 in Northern Sierra Leone despite a new pathogenic HIV2 emerging from this region. Data on ART treatment coverage is also lacking. Subjects presenting for voluntary HIV test and those referred by healthcare providers were enrolled following informed consent. This represents a targeted, higher risk population than the general population. Commercial HIV1/2 rapid tests were used in the field. PCR and NGS methods are being used to determine prevalence of newly emerging HIV-2F. A questionnaire was administered to collect demographic information and treatment history in those testing positive. Currently the prevalence of HIV in the targeted sample population is 5.98%. Interestingly, when compared to the last published data on HIV-2 in the region, prevalence has increased by a factor of 32, from 0.021 to 0.68%. 77% of HIV positive persons were newly identified cases. Of those previously testing HIV positive, only 41% were currently on treatment compared to 61% ART coverage in HIV positive persons in low and middle-income countries globally. Our data indicate the prevalence of HIV has increased in Sierra Leone since the civil war. Further data are needed to conclusively show prevalence changes of HIV in Northern Sierra Leone on a population level. The data also show that ART treatment rates in Northern Sierra Leone are significantly lower than the global average highlighting the need for improved case identification and treatment provision in this resource poor setting. Sequencing of HIV positive samples to determine the subtype is in process. This study provides a basis for further population based study of the HIV strains circulating in Northern Sierra Leone.